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A horn-like nodule developed in the middle of the forehead of a white rat, exposed perinatally to T-2 toxin and to zearalenone, the secondary metabolites of Fusarium. The hard nodule consisted mainly of keratine, derived from a squamous carcinoma spreading through the nasal turbinals and invading the brain.
This study is designed to establish a pulmonary tumor model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma cell (LLC) suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 sec per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph nodes metastasis were observed in all mice that were succeeded to form a lung nodule after intrapulmonary implantation. The size of tumor nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21 +/- 2 days (range; 19-24 days). Histopathological analysis revealed that no metastatic tumor was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary implantation is due to the release of tumor cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of CDDP on day 1 after tumor implantation tended to suppress the primary tumor nodule and significantly inhibited the lymph node metastasis. Thus, a solitary pulmonary tumor nodule model with lymph node metastasis approximates clinical lung cancer, and may provide a useful basis for lung cancer research.
Strains of Rhizobium leguminosarum (R.l.) biovar viciae containing pss mutations fail to make the acidic exopolysaccharides (EPS) and are unable to nodulate peas. It was found that they also failed to nodulate Vicia hirsuta, another host of this biovar. When peas were co-inoculated with pss mutant derivatives of a strain of R.l. by viciae containing a sym plasmid plus a cured strain lacking a sym plasmid (and which is thus Nod-, but for different reasons) but which makes the acidic EPS, normal numbers of nodules were formed, the majority of which failed to fix nitrogen (the occasional Fix+ nodules were presumably induced by strains that arose as a result of genetic exchange between cells of the two inoculants in the rhizosphere). Bacteria from the Fix- nodules contained, exclusively, the strain lacking its sym plasmid. When pss mutant strains were co-inoculated with a Nod- strain with a mutation in the regulatory gene nodD (which is on the sym plasmid pRL1JI), normal numbers of Fix+ nodules were formed, all of which were occupied solely by the nodD mutant strain. Since a mutation in nodD abolishes activation of other nod genes required for early stages of infection, these nod genes appear to be dispensable for subsequent stages in nodule development. Recombinant plasmids, containing cloned pss genes, overcame the inhibitory effects of psi, a gene which when cloned in the plasmid vector pKT230, inhibits both EPS production and nodulation ability. Determination of the sequence of the pss DNA showed that one, or perhaps two, genes are required for correcting strains that either carry pss mutations or contain multi-copy psi.(ABSTRACT TRUNCATED AT 250 WORDS)
This work describes an approach to monitor chondrogenesis of stage-24 chick limb mesodermal cells in vitro by analyzing the onset of type II collagen synthesis with carboxymethyl-cellulose chromatography, immunofluorescence, and radioimmunoassay. This procedure allowed specific and quantitative determination of chondrocytes in the presence of fibroblasts and myoblasts, both of which synthesize type I collagen. Chondrogenesis was studied in high-density cell preparations on tissue culture plastic dishes and on agar base. It was found that stage-24 limb mesenchymal cells initially synthesized only type I collagen. With the onset of chondrogenesis, a gradual transition to type II collagen synthesis was observed. In cell aggregates formed over agar, type II collagen synthesis started after 1 day in culture and reached levels of 80-90 percent of the total collagen synthesis at 6-8 days. At that time, the cells in the center of the aggregates had acquired the typical chondrocyte phenotype and stained only with type II collagen antibodies, whereas the peripheral cells had developed into a "perichondrium" and stained with type I and type II collagen antibodies. On plastic dishes plated with 5 X 10(6) cells per 35mm dish, cartilage nodules developed after 4-6 days, but the type II collagen synthesis only reached levels of 10-20 percent of the total collagen. The majority of the cells differentiated into fibroblasts and myoblasts and synthesized type I collagen. These studies demonstrate that analysis of cell specific types of collagen provides a useful method for detailing the specific events in the differentiation of mesenchymal cells in vitro.
We investigated the capacity of a clonal osteogenic cell line MC3T3-E1, established from newborn mouse calvaria and selected on the basis of high alkaline phosphatase (ALP) activity in the confluent state, to differentiate into osteoblasts and mineralize in vitro. The cells in the growing state showed a fibroblastic morphology and grew to form multiple layers. On day 21, clusters of cells exhibiting typical osteoblastic morphology were found in osmiophilic nodular regions. Such nodules increased in number and size with incubation time and became easily identifiable with the naked eye by day 40-50. In the central part of well-developed nodules, osteocytes were embedded in heavily mineralized bone matrix. Osteoblasts were arranged at the periphery of the bone spicules and were surrounded by lysosome-rich cells and a fibroblastic cell layer. Numerous matrix vesicles were scattered around the osteoblasts and young osteocytes. Matrix vesicles and plasma membranes of osteoblasts, young osteocytes, and lysosome-rich cells showed strong reaction to cytochemical stainings for ALP activity and calcium ions. Minerals were initially localized in the matrix vesicles and then deposited on well-banded collagen fibrils. Deposited minerals consisted exclusively of calcium and phosphorus, and some of the crystals had matured into hydroxyapatite crystals. These results indicate that MC3T3-E1 cells have the capacity to differentiate into osteoblasts and osteocytes and to form calcified bone tissue in vitro.
A promoter tagging program in the legume Lotus japonicus was initiated to identify plant genes involved in the nitrogen-fixing symbiosis between legumes and rhizobia. Seven transformed plant lines expressing the promoterless reporter gene uidA (beta-glucuronidase; GUS) specifically in roots and/or nodules were identified. Four of these expressed GUS in the roots only after inoculation with nodule-forming Mesorhizobium loti. In one line (T90), GUS activity was found in the root epidermis, including root hairs. During seedling growth, GUS expression gradually became focused in developing nodules and disappeared from root tissue. No GUS activity was detected when a non-nodulating mutant of M. loti was used to inoculate the plants. The T-DNA insertion in this plant line was located 1.3 kb upstream of a putative coding sequence with strong homology to calcium-binding proteins. Four motifs were identified, which were very similar to the "EF hands" in calmodulin-related proteins, each binding one Ca2+. We have named the gene LjCbp1 (calcium-binding protein). Northern (RNA) analyses showed that this gene is expressed specifically in roots of L. japonicus. Expression was reduced in roots inoculated with non-nodulating M. loti mutants and in progeny homozygous for the T-DNA insertion, suggesting a link between the T-DNA insertion and this gene.
In eukaryotes, diverse mRNAs containing only short open reading frames (sORF-mRNAs) are induced at specific stages of development. Their mechanisms of action may involve the RNA itself and/or sORF-encoded oligopeptides. Enod40 genes code for highly structured plant sORF-mRNAs involved in root nodule organogenesis. A novel RNA binding protein interacting with the enod40 RNA, MtRBP1 (for Medicago truncatula RNA Binding Protein 1), was identified using a yeast three-hybrid screening. Immunolocalization studies and use of a MtRBP1-DsRed2 fluorescent protein fusion showed that MtRBP1 localized to nuclear speckles in plant cells but was exported into the cytoplasm during nodule development in enod40-expressing cells. Direct involvement of the enod40 RNA in MtRBP1 relocalization into cytoplasmic granules was shown using a transient expression assay. Using a (green fluorescent protein)/MS2 bacteriophage system to tag the enod40 RNA, we detected in vivo colocalization of the enod40 RNA and MtRBP1 in these granules. This in vivo approach to monitor RNA-protein interactions allowed us to demonstrate that cytoplasmic relocalization of nuclear proteins is an RNA-mediated cellular function of a sORF-mRNA.
The animal pathogen Brucella abortus contains a gene cgt, which complemented Sinorhizobium meliloti nodule development (ndvA) and Agrobacterium tumefaciens chromosomal virulence (chvA) mutants. Complemented strains recovered the presence of anionic cyclic beta-1,2-glucan, motility, tumor induction in A. tumefaciens, and nodule occupancy in S. meliloti, all traits strictly associated with the presence of cyclic beta-1,2-glucan in the periplasm. Nucleotide sequencing revealed that B. abortus cgt contains a 1,797-bp open reading frame coding for a predicted membrane protein of 599 amino acids (65.9 kDa) that is 58.5 and 59.9% identical to S. meliloti NdvA and A. tumefaciens ChvA, respectively. Additionally, B. abortus cgt, like S. meliloti ndvA and A. tumefaciens chvA possesses ATP-binding motifs and the ABC signature domain features of a typical ABC transporter. Characterization of Cgt was carried out by the construction of null mutants in B. abortus 2308 and S19 backgrounds. Both mutants do not transport cyclic beta-1,2-glucan to the periplasm, as shown by the absence of anionic cyclic glucan, and they display reduced virulence in mice and defective intracellular multiplication in HeLa cells. These results suggest that cyclic beta-1,2-glucan must be transported into the periplasmatic space to exert its action as a virulence factor.
We describe a case of classic Kaposi's sarcoma (KS) in an Italian HIV-negative patient, with bone involvement and progression to anaplastic histotype. At the age of 22, violaceous patches of KS appeared on his feet. At the age of 50, he noted the appearance of a violaceous firm nodule on his right wrist. The lesions grew rapidly and became ulcerated. Radiotherapy led to a complete remission of symptoms. At the age of 55, a subcutaneous nodule developed on the proximal third of the right forearm associated with a wide painful edema of the right forearm and the proximal third of the right arm. The nodule enlarged rapidly, and an X-ray of the right forearm revealed the presence of a large osteolytic area of the ulna. A biopsy specimen from the right ulna showed bone erosion by a mesenchymal neoplasia with a high degree of malignancy. The right arm was amputated, and histologic examination of the surgical material confirmed the diagnosis of undifferentiated spindle-cell malignant neoplasia strongly positive for factor-VII-related antigen and CD34 antigen. Three years after surgical treatment, no recurrences have been observed.
OBJECTIVE: To ascertain the clinical effect of discontinuation of thyroxine (T4) suppression therapy in patients with solitary thyroid nodules or multinodular goiters (MNGs). METHODS: After long-term T4 suppression therapy was discontinued (desuppression) in 63 patients (45 with solitary or dominant nodules and 18 with MNGs), we conducted a prospective follow-up for a mean of 18 months in an effort to detect any thyroid-related changes. RESULTS: A dominant nodule developed in 4 of 18 patients with MNGs. Fine-needle aspirations showed benign lesions in these four patients, but two were referred for thyroidectomy because of substantial nodule growth (both lesions proved to be benign). Of the 45 patients with solitary or dominant thyroid nodules, 4 were lost to follow-up, and 9 had clinically significant nodule enlargement and underwent thyroidectomy. One patient had clinically significant papillary carcinoma, and one had microscopic papillary carcinoma. CONCLUSION: These data on effect of discontinuation of T4 suppression therapy suggest that (1) about 20% of patients with MNGs will ultimately have thyroid nodule enlargement and (2) about 20% of patients with a solitary or dominant nodule will have nodule enlargement, of which approximately 20% will have papillary carcinoma.
Symbiotic nitrogen fixation is beneficial to legumes. Excessive nodule development, however, disturbs the host growth by over-consuming energy from the plant. To keep a balance, legumes possess a systemic negative feedback regulatory system called 'autoregulation of nodulation', which controls the nodule number and the nodulation zone through long-distance signaling. Plants that are deficient in autoregulation display a hypernodulating phenotype. Recently, genes encoding a CLAVATA1-like receptor-like kinase that mediates autoregulation of nodulation have been identified from several legumes, such as Lotus japonicus and soybean. Other hypernodulation mutants that are regulated by shoot or root genotypes have also been isolated.
Gene expression profiles during early stages of formation of symbiotic nitrogen-fixing nodules in a model legume Lotus japonicus were analyzed by means of a cDNA array of 18,144 non-redundant expressed sequence tags (ESTs) isolated from L. japonicus. Expression of a total of 1,076 genes was significantly accelerated during the successive stages that represent infection of Mesorhizobium loti, nodule primordium initiation, nodule organogenesis, and the onset of nitrogen fixation. These include 32 nodulin and nodulinhomolog genes as well as a number of genes involved in the catabolism of photosynthates and assimilation of fixed nitrogen that were previously known to be abundantly expressed in root nodules of many legumes. We also identified a large number of novel nodule-specific or enhanced genes, which include genes involved in many cellular processes such as membrane transport, defense responses, phytohormone synthesis and responses, signal transduction, cell wall synthesis, and transcriptional regulation. Notably, our data indicate that the gene expression profile in early steps of Rhizobium-legume interactions is considerably different from that in subsequent stages of nodule development. A number of genes involved in the defense responses to pathogens and other stresses were induced abundantly in the infection process, but their expression was suppressed during subsequent nodule formation. The results provide a comprehensive data source for investigation of molecular mechanisms underlying nodulation and symbiotic nitrogen fixation.
Keratosis lichenoides chronica (KLC) is a rare chronic disease characterized by violaceous, papular and nodular lesions typically arranged in a linear and reticulate pattern. The etiology of KLC is unknown, but it may be associated with internal diseases such as hypothyroidism, glomerulonephritis and lymphoproliferative disorders. Herein, we describe the case of 44-year-old male patient with characteristic lesions of KLC on the trunk and extremities, present for 12 years. The clinical diagnosis was proven by histopathological examination on several occasions. In the years following the diagnosis of KLC, he developed bilateral hilar and multiple mediastinal, cervical and inguinal lymphadenopathies and hepatosplenomegaly. In 2000, diffuse interstitial and then reticulonodular pulmonary infiltrates associated with fever, weight loss, malaise and subcutaneous nodules developed. Biopsies taken from peripheral and mediastinal lymph nodes, pulmonary parenchyma, pleural tissue, bone marrow and skin showed non-necrotizing granulomas, indicating a sarcoidal granulomatous reaction. Characteristic histopathological findings and the absence of atypical cells, clonality and a high proliferative index excluded lymphomas. Furthermore, detailed tests showed no evidence of an infectious granulomatous disease. As far as we know, this is the first reported case of KLC associated with a sarcoidal granulomatous reaction.
The biology of O. flexuosa was studied during the examination of numerous subcutaneous nodules, which were taken from the hides of red deer of all age-classes. In fawns the development of the nodule is induced by the immature stages, probably by the females. At the same time a hematome is formed. Males of different ages penetrate into the nodule where mature or immature females are present. Later they mate and remain within the nodule until the microfilariae in the uteri of the females develop. Usually 1 or 2, occasionally 4 females are found together. During the development of the embryos in the uteri the initially stretched female winds up. Only a short anterior part remains always straight. It is put out through the wall of the capsule in order to release the microfilariae. The males are often the majority reaching to 13 in one nodule. During the release of the microfilariae the males are found outside the nodule on the surface or near-by in the subcutaneous connective tissue. Both sexes are able to mate a second time. In older deer the males are also able to induce the development of nodules.
BACKGROUND: The risk of thyroid carcinoma in patients with Graves disease has been particularly emphasized when nodules coexist with thyroid hyperplasia; a surgical approach has been suggested. OBJECTIVES: To detect thyroid nodules early in patients with Graves disease and to evaluate the risk of carcinoma. METHODS: The study group included 315 consecutive outpatients with Graves hyperthyroidism not previously treated with surgery or radioiodine therapy. Thyroid ultrasonography was performed at the time of enrollment and repeated annually in all patients; fine-needle aspiration (FNA) was carried out in those patients with nodules and repeated after 2 years or at shorter intervals. RESULTS: One hundred six of 315 patients with Graves disease had thyroid nodules 8 mm in diameter or larger detected by ultrasonography. In 49 patients, nodules were present at the time of the first examination; in 57 patients, nodules developed during follow-up. Fine-needle aspiration cytology results revealed features of carcinoma in only 1 patient; this was confirmed by histologic examination of excised thyroid tissue. The nodules with normal cytologic features at the time of the first examination did not show any clinical and/or cytologic evolution toward malignancy during follow-up. CONCLUSIONS: Ultrasonographic evidence of nodules was frequently found among our patients with Graves disease, but malignant FNA cytologic findings of the examined nodules were rare at the time of diagnosis and throughout the course of the disease. When FNA cytologic evaluation does not indicate malignancy, the presence of thyroid nodules in patients with Graves disease does not indicate an aggressive therapeutic approach.
The relationship between CCl4 or (CCl4 + phenobarbital)-induced liver cirrhosis and diethylnitrosamine (DEN) hepatocarcinogenesis in male F-344 rats was investigated. DEN given alone produced no liver lesions after 16 weeks, but 4/12 (33%) neoplastic nodules developed when nitrosamine was administered to rats with previously established cirrhosis. On the other hand, (CCl4 + phenobarbital) post-treatment had an even stronger effect, increasing the yield of neoplastic nodules to 100% (28/28). Since the exposure time of DEN was the same in all treated groups (4 months), the results indicate the decreased effectiveness of (CCl4 + phenobarbital) pretreatment on DEN hepatocarcinogenesis.
In a 64-year-old woman, a solitary pulmonary nodule developed 30 months after combination chemotherapy and thoracic irradiation had been administered for small-cell carcinoma of the ipsilateral lung. No evidence of extrapulmonary tumor was identified, and the nodule was excised. The well-circumscribed tumor had histologic features of a malignant ependymoma. Immunohistochemical staining showed strong reactivity for glial fibrillary acidic protein; staining for S-100 protein, Leu-7, and vimentin was less intense. Focal reactivity for epithelial membrane antigen was also present. Stains for keratin, synaptophysin, and chromogranin were negative. Electron microscopy showed cohesive cells, the cytoplasm of which contained intermediate filaments. Rare well-formed junctions were also noted. Flow cytometry of formalin-fixed paraffin-embedded tissue demonstrated DNA aneuploidy. Six months after the ependymoma was diagnosed, the patient, who had a history of hypertension, died of an intracerebral hemorrhage.
Patellofemoral pain due to an unusual suprapatellar fibrous nodule developed in three patients after posterior stabilized total knee arthroplasty. Each patient had a "catch" or "clunk" associated with pain on extension of the knee. At revision, a prominent fibrous nodule was found at the junction of the proximal patellar pole and the quadriceps tendon. The pathogenesis of this proximal fibrous nodule may involve impingement of the anterosuperior edge of the intercondylar notch area of the femoral component into the proximal quadriceps tendon or may involve impingement of the patellar prosthesis itself on the quadriceps tendon. Roentgenographic examination revealed an abnormally proximal placement of the patellar prosthesis on the patella. Surgical removal of the fibrous nodule resolved the symptoms. Revision of the patellar prosthesis may be necessary.